In this program of clinical and basic neuropharmacological research, we shall continue to explore the biochemical pathophysiology of the affective disorders. The long-term objective of this research is the development of a clinically and therapeutically relevant classification of depressive disorders based on differences in the biochemical pathophysiology of different types of depressions. The use of biochemical criteria as predictors of response to specific forms of antidepressant pharmacotherapy will be studied in this project. Moreover, we shall explore possible animal models of the specific biochemical subgroups of depressive disorders identified in the ongoing clinical studies.